Adaptive Immune Repsonse Part 1 - Recognition

Question 1

Key players in adaptive immunity

Answer 1

Naive T cells are only activated when there is an antigen presenting cell present - so presence of tumor cells and pathogens dont activate Naive T cells on their own

APC have receptors that bind to pathogens and present them to T cells, which activates them

APC - sense the pathogen, capture it, process it and then present it

Question 2

Different types of antigen presenting cell (APC)

Answer 2

Dendritic Cells - present pathogen to Naive T cells (cells not be exposed to an/the antigen) - function - T cell response against most pathogens

Langerhans cells - present pathogen to Naive T cells - function T cell response against most pathogens - specifically in the skin

Macrophages - present pathogen to Effector T cells (these are naive T cells that have been activated by the two cells above that look for macrophage or B cells) - function Phagocytic activities

B cells - present pathogen to Effector T cells (need effector T cells to produce IgM (when exposed to antigen for first time, if exposed from the first time then the body switches to IgG)) - antibody response

Naïve T cells = T cells that have not previously encountered the antigen

Effector T cells = T cells that have previously encountered the antigen and are capable of performing effector functions during an immune response

Question 3

Features of antigen presenting cells

Answer 3

Strategic location
	Mucosal membranes (gut, lung) 	
	Skin (i.e., Langerhans cells) 
	Blood (i.e., plasmacytoid cells) 	
	Lymph nodes (i.e., follicular dendritic cells) 
	Spleen

Diversity in pathogen sensors (PRRs)
	Extracellular pathogens (bacteria, fungi, protozoa)
	Intracellular pathogens (viruses)

Diversity in pathogen capture mechanisms
Phagocytosis (whole microbe)
Macropinocytosis (soluble particles)

Question 4

Examples of PRRs that can sense different types of IC and EC pathogens

Answer 4

Present at the cell surface - named according to what they recognise (TLR1-TLR11)

They are also present inside the cell as viruses can get inside the cell - from there the virus exposes its genetic material that can be sensed by TLR3/7/9

TLR4 - key to remember as it is involved in sepsis development
TLR1 and TLR2 detects gram positive Staph aureus and Strep pneumonia
TLR4 and TLR5 detects meningitis and E.coli
TLR8 and TLR9 detect adenovirus and norovirus inside the cell

Process -

1) microbes breach under the skin
2) macrophage starts innate immunity
3) APC pick up microbe and use lymphatic system to go to nearest lymphoid tissue (as have max number of B and T cells)
4) Depening on type of interaction you will activate either a humoral response (if its a EC microbe), or cell mediated response (if its a IC microbe)

Question 5

Pathogens are presented by major histocompatibility complex (MHC) molecules)

Answer 5

MHC class 2 molecules - expressed on APC, dendritic cells, macrophages and B cells 
MHC class 1 molecules - expressed on all nucleated cells

Key features of MHC class I and class II molecules - Co-dominant expression - Both MHC class I and II parental molecules are co-expressed in each individual (6 of each class)

Polymorphic genes (different alleles) - Different individuals present and respond to different microbes

Presentation of microbial peptides
Antigen presenting cells present intracellular microbes via MHC Class I molecules (HLA-A, B and C)
Antigen presenting cells present extracellular microbes via MHC Class II molecules (HLA-DP, DQ, DR)

Question 6

Processing of intracellular microbes - endogenous pathway

Answer 6

Viral protein present in the cytosol

Marked for destruction by the proteasome

Proteasome-generated viral peptide transported to ER by TAP proteins

Formation of viral peptide-MHC class I complex if right match

Occurs in all cell types

APCs and non-APCs present peptides from intracellular pathogens to CD8+ T cells

Question 7

Processing of extra cellular microbes - exogenous pathway

Answer 7

Microbes captured by phagocytosis or micropinocytosis

Degradation in small peptides in the endosome

Peptide-rich vesicles fuse with vesicles containing MHC class II molecules

Formation of peptide-MHC class II complex if right match

Occurs only in antigen-presenting cells including dendritic cells, B cells and macrophages

APCs presents peptides extracellular pathogens to CD4+ T cells

Question 8

Peptide presentation by MHC class 1 and class 2 molecules

Answer 8

Peptide binding cleft - Variable region with highly polymorphic

Broad specificity - Many peptides presented by the same MHC molecule

Responsive T cells - MHC class I recognized by CD8+ molecules on T cells - MHC class II recognized by CD4+ molecules on T cells

Question 9

Clinical importance of MHC molecules

Answer 9

Host can deal with a variety of microbes
- Gene families
- Genetic polymorphism
No two individuals have the same set of MHC molecules - This means that we don’t get wiped out by a single microbe/epidemic disease

Different people will have different susceptibilities to infections - Strong vs weak immune response against infectious microbes

Clinical importance of MHC molecules
Patient 1 - A 27 year old male - History of injection drug use - Opportunistic infections - Immunodeficiency = CD4+ T cell count <200 cell/